Human Parainfluenza Virus 3 Infection in a Novel Human Lung Tissue Model PROJECT SUMMARY: Human parainfluenza virus 3 (HPIV3) constitutes a major public health concern in the United States as it is the second largest cause of hospitalization in children under the age of five and responsible for high morbidity and mortality in immunocompromised adults. Studying HPIV3 has traditionally been conducted using cell lines, small rodent models, and human airway epithelial cell culture models, all of which have limitations with regards to their ability to provide insights into human disease in the lung. To address this gap in knowledge, we have developed a novel lung model using whole human lung tissue explants. In preliminary data, we utilized a recombinant GFP-reporter HPIV3 to infect human lung tissue explants and show that HPIV3 can replicate robustly in this system. We hypothesize that evaluation of HPIV3 infection in this human lung tissue model will elucidate novel virus:host interactions and provide insights into the pathogenesis of HPIV3 in humans. In Aim 1, we will immunophenotype the HPIV3-infected cells in human lung tissue. In Aim 2, we will characterize the inflammatory response induced by HPIV3 and determine whether inflammation is driven by infected cells or bystander cells.